DESCRIPTION: Although cocaine addiction and overdose represent a significant health problem in the United States, there is currently no available pharmacologic treatment. This Phase I proposal is aimed at testing a large number of compounds using a high throughput screening (HTS) technique to find selective cocaine antagonists or agonist/ antagonists that may be useful in treating cocaine addiction and overdose. Compounds from in vitro binding and uptake studies will be used in in vivo behavior tests to identify potentially useful compounds.